The use of alkylene glycols or monoalkyl ethers thereof, either alone or in combination with other vehicle components, as carriers for medicaments, such as steroids or prostaglandins, is well-known. See, for example, Great Britain Pat. No. 1,133,800; South African Pat. No. 70/04245; and U.S. Pat. Nos. 2,600,344; 2,856,329; 3,069,322; 3,592,222; 3,592,930; and 3,673,213. Such carriers, however, do not, in general, provide requisite stabilizing properties for the medicament material. That is, after relatively short storage times, the chemical potency of the active medicament had degraded significantly to a point where the preparation, if taken at the recommended dosage level, might be of insufficient activity to accomplish the desired therapeutic objective.
Of particular interest in the present invention are the family of materials known as prostaglandins. Prostaglandins are a group of chemically related 20-carbon chain hydroxy fatty acids having the basic skeleton of prostanoic acids: ##STR1##
The prostaglandins having a hydroxy group at the C-11 position and a keto group at the C-9 position are known as the PGE series. Those having a hydroxyl group in place of the keto group at the C-9 position are known as the PGF series and are further designated by an .alpha. or .beta. suffix to indicate the configuration of the hydroxyl group at the C-9 position. The natural compounds are the .alpha.-hydroxy substituted compounds. They may contain different degrees of unsaturation in the molecule, particularly at C-5, C-13, and C-17, the unsaturation is also indicated by a suffix. Thus, for example, PGE.sub.1 refers to a prostanoic acid having a trans olefin bond at the 13-position. For a review on prostaglandins and the definition of primary prostaglandins, see, for example, S. Bergstrom, Recent Progress in Hormone Research 22, pp. 153-175 (1966) and S. Bergstrom, Science 157, page 382 (1967).
Using accepted nomenclature, prostaglandins of the PGE, PGF, PGA and PGB series are named as follows:
Pge.sub.1 : 11.alpha.,15.alpha.-dihydroxy-9-keto-13-prostenoic acid; PA1 Pge.sub.2 : 11.alpha.,15.alpha.-dihydroxy-9-keto-5,13-prostadienoic acid; PA1 Pge.sub.3 : 11.alpha.,15.alpha.-dihydroxy-9-keto-5,13-17-prostatrienoic acid; PA1 Pgf.sub.1 : 9.alpha.,11.alpha.,15.alpha.-trihydroxy-13-prostenoic acid; PA1 Pgf.sub.2 : 9.alpha.,11.alpha.,15.alpha.-trihydroxy-5,13-prostadienoic acid; PA1 Pga.sub.1 : 15.alpha.-hydroxy-9-keto-10,15-prostadienoic acid; PA1 Pga.sub.2 : 15.alpha.-hydroxy-9-keto-10,13,17-prostatrienoic acid; PA1 Pgb.sub.1 : 15.alpha.-hydroxy-9-keto-8,13-prostadienoic acid; and, PA1 Pgb.sub.2 : 15.alpha.-hydroxy-9-keto-10,13,17-prostatrienoic acid.
Prostaglandins are widely distributed in mammalian tissues and have been isolated from natural sources in very small amounts. In addition a number of the natural occurring prostaglandins have been prepared by chemical synthesis; see for example, J. Am. Chem. Soc. 91, 5675 (1969), J. Am. Chem. Soc. 92, 2586 (1970), J. Am. Chem. Soc. 93, 1489-1493 (1971) and references cited therein, W. P. Schneider et al, J. Am. Chem Soc. 90, 5895 (1968), U. Axen et al., Chem. Commun., 303 (1969), and W. P. Schneider, Chem. Commun. 304 (1969).
Because of the remarkable range of biological and pharmacological properties exhibited by this family of compounds, a great deal of interest has focused upon such compounds. It is known, however, that prostaglandins in general, and specifically PGE.sub.2, are, from a chemical point of view, relatively unstable. See, for example, Brummer J. Pharm. Pharmac. 23, 804 (1971), and Karim et al., European J. Pharmacol. 4, 416 (1968). It would, therefore, be desirable to have a prostaglandin preparation wherein the prostaglandin material is stabilized by the vehicle material.